SERUM-PROTEIN BINDING OF PROPOFOL IN PATIENTS WITH RENAL-FAILURE OR HEPATIC CIRRHOSIS

Background: Serum protein binding is a limiting factor in the access o f drugs to the central nervous system. Disease-induced modifications o f the degree of binding may influence the effect of anesthetic drugs. Methods: The protein binding of propofol, an intravenous anaesthetic a gent which is highly bound to serum albumin, has been investigated in serum samples from healthy volunteers, from patients with chronic rena l failure not undergoing hemodialysis, from patients with chronic rena l failure included in a regular hemodialysis program, and from patient s with hepatic cirrhosis. Protein binding was determined by the ultraf iltration technique using an Amicon Micropartition System, MPS-1. Resu lts: The percentage of unbound propofol (mean(SD)) in healthy voluntee rs (n=16) was 0.98 (0.48) % showing a high interindividual variability . Chronic renal failure did not significantly modify serum protein bin ding of propofol. In the chronic renal failure group not undergoing re gular hemodialysis (n=9), unbound propofol was 0.92 (0.34) %. In addit ion, patients in periodic dialysis did not show changes in propofol bi nding either compared before (1.11 (0.33) %; n=13) or after hemodialys is (0.87 (0.38) %; n=12). A slight decrease in albumin concentration w as found in all renal patients (P<0.05) in comparison to healthy volun teers. Creatinine and urea concentrations were higher in these patient s (P<0.01) but in the postdialysis group, the differences in urea leve ls were not significant when compared with those of volunteers. No cha nges in the degree of propofol binding were observed in patients with hepatic cirrhosis (0.97 (0.30) %; n=14) when compared with the group o f healthy volunteers. Significant differences were observed in albumin (P<0.01) and bilirubin (P<0.05) concentrations. Considering all subje cts, the degree of binding did not correlate with biomedical data. Con clusion: Due to the the absence of significant changes in the protein binding it is unlikely that there will be an exaggerated pharmacologic al response in patients with renal and hepatic disease following the a dministration of a standard propofol dose, although due to interpatien t variability careful titration can be recommended.